Drug Delivery Device Inner Housing Having Helical Spline

ABSTRACT

A dose setting mechanism for a drug delivery device is disclosed. The mechanism comprises an outer housing and an inner housing having an external groove and a helical spline. The inner housing helical spline guides a driver to dispense a set dose. A dial sleeve is disposed between the outer and inner housing and is rotatably engaged with the inner housing. When a dose is set, the dial sleeve is rotated and translates away from both the outer housing and the inner housing.

BACKGROUND

1. Field of the Present Patent Application

The present application is generally directed to dose setting mechanismsfor drug delivery devices. More particularly, the present application isgenerally directed to a dose setting mechanism comprising an innerhousing having a helical spline and used for drug delivery devices.Aspects of the invention may be equally applicable in other scenarios aswell.

2. Background

Pen type drug delivery devices have application where regular injectionby persons without formal medical training occurs. This may beincreasingly common among patients having diabetes where self-treatmentenables such patients to conduct effective management of their disease.

There are basically two types of pen type delivery devices: resettabledevices (i.e., reusable) and non-resettable (i.e., disposable). Thesetypes of pen delivery devices (so named because they often resemble anenlarged fountain pen) are generally comprised of three primaryelements: (i) a cartridge section that includes a cartridge oftencontained within a housing or holder; (ii) a needle assembly connectedto one end of the cartridge section; and (iii) a dosing sectionconnected to the other end of the cartridge section. A cartridge (oftenreferred to as an ampoule) typically includes a reservoir that is filledwith a medication (e.g., insulin), a movable rubber type bung or stopperlocated at one end of the cartridge reservoir, and a top having apierceable rubber seal located at the other, often necked-down, end. Acrimped annular metal band is typically used to hold the rubber seal inplace. While the cartridge housing may be typically made of plastic,cartridge reservoirs have historically been made of glass.

The needle assembly is typically a replaceable double-ended needleassembly. Before an injection, a replaceable double-ended needleassembly is attached to one end of the cartridge assembly, a dose isset, and then a dose is administered. Such removable needle assembliesmay be threaded onto, or pushed (i.e., snapped) onto the pierceable sealend of the cartridge assembly.

The dosing section or dose setting mechanism is typically the portion ofthe pen device that is used to set a dose. During an injection, aspindle contained within the dose setting mechanism presses against thebung or stopper of the cartridge. This force causes the medicationcontained within the cartridge to be injected through an attached needleassembly. After an injection, as generally recommended by most drugdelivery device and/or needle assembly manufacturers and suppliers, theneedle assembly is removed and discarded.

Different types of pen delivery devices, including disposable (i.e.,non-resettable) and reusable (i.e., resettable) varieties, have evolvedover the years. For example, disposable pen delivery devices aresupplied as self-contained devices. Such self-contained devices do nothave removable pre-filled cartridges. Rather, the pre-filled cartridgesmay not be removed and replaced from these devices without destroyingthe device itself. Consequently, such disposable devices need not have aresettable dose setting mechanism.

In contrast to typical disposable pen type devices, typical reusable pendelivery devices feature essentially two main reusable components: acartridge holder and a dose setting mechanism. After a cartridge isinserted into the cartridge holder, this cartridge holder is attached tothe dose setting mechanism. The user uses the dose setting mechanism toselect a dose. Before the user injects the set dose, a replaceabledouble-ended needle assembly is attached to the cartridge housing. Thisneedle assembly may be threaded onto or pushed onto (i.e., snapped onto)a distal end of the cartridge housing. In this manner, a double endedneedle mounted on the needle assembly penetrated through a pierceableseal at a distal end of the cartridge. After an injection, the needleassembly is removed and discarded. After the insulin in the cartridgehas been exhausted, the user detaches the cartridge housing from thedose setting mechanism. The user can then remove the empty cartridgefrom the cartridge retainer and replace the empty cartridge with a new(filled) cartridge. Aside from replacing the empty cartridge with a newcartridge, the user must somehow prepare the dose setting mechanism fora new cartridge: the dose setting mechanism must be reset to a startingor initial position. For example, in certain typical resettable devices,in order to reset the dose setting mechanism, the spindle that advancesin a distal direction during dose injection must somehow be retractedback into the dose setting mechanism. Certain known methods ofretracting this spindle back into the dose setting mechanism to arestart or an initial position are known in the art. As just oneexample, certain known reset mechanisms require a user to turn back orpush back (retract) the spindle or some other portion of the dosesetting mechanism. Resetting of known dose setting mechanisms havecertain perceived disadvantages. One perceived disadvantage is that thepen device user has to disassemble the device to either remove an emptycartridge or somehow reset the device. As such, another perceiveddisadvantage is that such devices have a high number of parts andtherefore such devices are typically complicated from a manufacturingand from an assembly standpoint. For example, certain typical resettablepen type devices are not intuitive as to how a user must replace anempty cartridge or how a user is to reset the device. In addition,because such resettable devices use a large number of components parts,such resettable devices tend to be large and bulky, and therefore noteasy to carry around or easy to conceal.

There is, therefore, a general need to take these disadvantagesassociated with resetting issues into consideration in the design anddevelopment of resettable drug delivery devices. Such desired drugdelivery devices would tend to reduce the number of component parts andalso tend to reduce manufacturing costs while also making the deviceless complex to assemble and manufacture. Such desired devices wouldalso tend to simplify the steps required for a user to reset a dosesetting mechanism while also making the device less complex and morecompact in size.

SUMMARY

According to an exemplary arrangement, a dose setting mechanism for adrug delivery device comprises an outer housing and an inner housinghaving an external groove and a helical groove. The inner housing guidesthe driver to dispense a dose set by the dose setting mechanism. A dialsleeve may be disposed between the outer and inner housing and isrotatably engaged with the inner housing. When a dose is set, the dialsleeve is rotated with respect to both the outer housing and the innerhousing. The dial sleeve is translated away from both the outer housingand the inner housing. These as well as other advantages of variousaspects of the present invention will become apparent to those ofordinary skill in the art by reading the following detailed description,with appropriate reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments are described herein with reference to thedrawings, in which:

FIG. 1 illustrates a first embodiment of a resettable drug deliverydevice;

FIG. 2 illustrates a sectional view of the first embodiment of the drugdelivery device illustrated in FIG. 1;

FIG. 3 illustrates a sectional view of the first embodiment of the drugdelivery device of FIG. 2 in a first position;

FIG. 4 illustrates a sectional view of the first embodiment of the drugdelivery device of FIG. 2 in a second position;

FIG. 5 illustrates a sectional view of the first embodiment of the drugdelivery device of FIG. 2 in a third position;

FIG. 6 illustrates a first arrangement of the driver illustrated inFIGS. 2-5 comprising a first driver portion and a second driver portion;

FIG. 7 illustrates a distal end of the spindle of the dose settingmechanism illustrated in FIGS. 2-5;

FIG. 8 illustrates a sectional view of a second embodiment of a dosesetting mechanism of the drug delivery device illustrated in FIG. 1;

FIG. 9 illustrates a partial sectional view of the second embodiment ofthe dose setting mechanism illustrated in FIG. 8;

FIG. 10 illustrates a close up view of Gap A illustrated in FIG. 8;

FIG. 11 illustrates a second arrangement of the driver illustrated inFIGS. 6-8 comprising a first driver portion and a second driver portion;

FIG. 12 illustrates the dose setting mechanism illustrated in eitherFIGS. 2-5 or FIGS. 6-8, and

FIG. 13 illustrates the dose setting mechanism illustrated in FIG. 12 inwhich a user has set a dose;

FIG. 14 illustrates a sectional view of another embodiment of a dosesetting mechanism of the drug delivery device illustrated in FIG. 1;

FIG. 15 illustrates a partial sectional view of the embodiment of thedose setting mechanism illustrated in FIG. 14;

FIG. 16 illustrates a partial view of yet another embodiment of a dosesetting mechanism of the drug delivery device illustrated in FIG. 1;

FIG. 17 illustrates the partial sectional view of embodiment of the dosesetting mechanism illustrated in FIG. 16 in a second position;

FIG. 18 illustrates the partial sectional view of embodiment of the dosesetting mechanism illustrated in FIG. 16 with a clicker portion removed;and

FIG. 19 illustrates a clicker portion that may be used with the dosesetting mechanism illustrated in FIG. 16

DETAILED DESCRIPTION

The terms “drug” or “medication” or “medicinal product” or “medicament”,as used herein, mean a pharmaceutical formulation containing at leastone pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Referring to FIG. 1, there is shown a drug delivery device 1 inaccordance with a first arrangement of the present invention. The drugdelivery device 1 comprises a housing having a first cartridge retainingpart 2, and dose setting mechanism 4. A first end of the cartridgeretaining part 2 and a second end of the dose setting mechanism 4 aresecured together by retaining features. In this illustrated arrangement,the cartridge retaining part 2 is secured within the second end of thedose setting mechanism 4. A removable cap 3 is releasably retained overa second end or distal end of a cartridge retaining part. As will bedescribed in greater detail, the dose setting mechanism 4 comprises adose dial grip 12 and a window or lens 14. To set a dose of medicationcontained within the drug delivery device 1, a user rotates the dosedial grip 12 and the window allows a user to view the dialed dose by wayof a dose scale arrangement 16. FIG. 2 illustrates the medical deliverydevice 1 of FIG. 1 with the cover 3 removed from the distal end of themedical delivery device. As illustrated, a cartridge 20 from which anumber of doses of a medicinal product may be dispensed is provided inthe cartridge housing 6. Preferably, the cartridge 20 contains a type ofmedicament that is administered often, such as once or more times a day.Once such medicament is insulin. A bung or stopper (not illustrated inFIG. 2) is retained in a first end or a proximal end of the cartridge20.

The dose setting mechanism 4 of the drug delivery device illustrated inFIG. 2 may be utilized as a reusable (and hence resettable) or anon-reusable (and hence non-resettable) drug delivery device. Where thedrug delivery device 1 comprises a reusable drug delivery device, thecartridge is removable from the cartridge housing 6. The cartridge 20may be removed from the device without destroying the device by merelythe user disconnecting the dose setting mechanism 4 from the cartridgeholder 20.

In use, once the removable cap 3 is removed, a user can attach asuitable needle assembly to the distal end of the cartridge holder. Suchneedle unit may be screwed onto a distal end of the housing oralternatively may be snapped onto this distal end. A replaceable cap 3is used to cover the cartridge holder 6 extending from the dose settingmechanism 4. Preferably, the outer dimensions of the replaceable cap 3are similar or identical to the outer dimensions of the dose settingmechanism 4 so as to provide an impression of a unitary whole when thereplaceable cap 3 is in position covering the cartridge holder 2.

FIG. 3 illustrates a sectional view of the dose setting mechanism 4removably connected to the cartridge holder 29. The dose settingmechanism 4 comprises an outer housing 40 containing a spindle 42, anumber sleeve 24, a clutch 26 a clicker 75, and a driver 30. A firsthelical groove 19 extends from a first end of a spindle 42. In onearrangement, the spindle 42 is of generally circular in cross sectionhowever other arrangements may also be used. The first end of thespindle 42 (a distal end 43 of the spindle 42) extends through apressure plate 64. A spindle bearing 50 is located at the distal end 43of the spindle 42. The spindle bearing 50 is disposed to abut a secondend of the cartridge piston 18. The driver 30 extends about the spindle42. The clutch 26 is disposed about the driver 30, between the driver 30and a number sleeve 24. The clutch 26 is located adjacent the second endof the driver 30. A number sleeve 24 is provided outside of the clutch26 and radially inward of the housing 40. The main housing 4 is providedwith a window 14 through which a part of an outer surface 11 of thenumber sleeve 10 may be viewed.

Returning to FIGS. 1-2, a dose dial grip 12 is disposed about an outersurface of the second end of the number sleeve 10. An outer diameter ofthe dose dial grip 12 preferably corresponds to the outer diameter ofthe housing 40. The dose dial grip 12 is secured to the number sleeve 10so as to prevent relative movement between these two components. In onepreferred arrangement, the dose dial grip 12 and number sleeve 10comprise a one piece component that is rotationally coupled to a clutchand drive sleeve and axially coupled to the number sleeve 10. However,alternative coupling arrangements may also be used.

Returning to FIGS. 3-5, in this arrangement, driver 30 comprises a firstdriver portion 44 and a second driver portion 46 and these portionsextend about the spindle 42. Both the first and the second driverportions 44, 46 are generally cylindrical. As can be seen from FIG. 6,the first drive portion 44 is provided at a first end with a firstradially extending flange 56. A second radially extending flange 58 isprovided spaced a distance along the first driver portion 44 from thefirst flange 56. An intermediate helical groove 62 is provided on anouter part of the first driver portion 44 extending between the firstflange 56 and the second flange 58. A portion or a part helical groove68 extends along an internal surface of the first driver portion 44. Thespindle 42 is adapted to work within this part helical groove 68.

A dose limiter 38 (illustrated in FIG. 3) is located between the driver30 and the housing 4, disposed between the first flange 56 and thesecond flange 58. In the illustrated arrangement, the dose limiter 38comprises a nut. The dose limiter 38 has an internal helical groovematching the helical groove 66 of the driver 30. In one preferredarrangement, the outer surface of the dose limiter 38 and an internalsurface of the housing 40 are keyed together by way of splines 65 a, 65b. In this preferred arrangement, splines 65 a, 65 b comprise linearsplines. This prevents relative rotation between the dose limiter 38 andthe housing 40 while allowing relative longitudinal movement betweenthese two components.

Referring back to FIGS. 2-5, essentially, in normal use, the operationof the dose setting mechanism 4 occurs as follows. To dial a dose in thearrangement illustrated in FIGS. 1-5, a user rotates the dose dial grip12. The driver 30, the clutch 26 and the number sleeve 10 rotate alongwith the dose dial grip 12. In this preferred arrangement, the clicker75 is disposed between a distal end of the clutch 26 and a flange 80 ofthe drive sleeve 46. The clicker 75 and the internal surface of thehousing 40 are keyed together by way of splines 65 a, 65 b. Thisprevents rotation of the clicker 75 with respect to the housing 40either during dose selection or during dose administration.

The number sleeve 10 extends in a proximal direction away from thehousing 40. In this manner, the driver 30 climbs the spindle 42. As thedriver 30 and the clutch rotates, a distal portion 23 of the clutchdrags over the clicker 75 to produce a click. Preferably, the distalportion includes a plurality of splines or features that are disposedsuch that each click corresponds to a conventional unit dose, or thelike.

At the limit of travel, a radial stop on the number sleeve 10 engageseither a first stop or a second stop provided on the housing 40 toprevent further movement. Rotation of the spindle 42 is prevented due tothe opposing directions of the overhauled and driven threads on thespindle 42. The dose limiter 38, keyed to the housing 40, is advancedalong the thread 66 by the rotation of the driver 30.

FIG. 2 illustrates the medical delivery device after a desired dose of79 International Units (IU) has been dialed. When this desired dose hasbeen dialed, the user may then dispense the desired dose of 79 IU bydepressing the dial grip. As the user depresses the dial grip 12, thisdisplaces the clutch 26 axially with respect to the number sleeve 10,causing the clutch 26 to disengage. However the clutch 26 remains keyedin rotation to the driver 30.

The driver 30 is prevented from rotating with respect to the mainhousing 4 but it is free to move axially with respect thereto. Thelongitudinal axial movement of the driver 30 causes the spindle 42 torotate and thereby to advance the piston 18 in the cartridge 20.

In normal use, the first and second portions 44, 46 of the driver 30 arecoupled together when the dose dial sleeve 10 is rotated. That is, innormal use, the first and second portions 44, 46 of the driver 30 arecoupled together with the dose dial sleeve 10 when a user sets a dose byturning the dose dial grip 12. After each dispensed dose, the spindle 42is pushed in a distal direction, acting on the bung 18 of the cartridge20 to continue to expel a dialed dose of medication out of an attachedneedle assembly releasably connected to the distal end 8 of thecartridge holder 6.

After a user uses the drug delivery device 1 to dispense all of themedication contained in the cartridge 20, the user may wish to replacethe empty cartridge in the cartridge holder 6 with a new cartridge. Theuser must then also reset the dose setting mechanism 4: for example, theuser must then retract or push the spindle 42 back into the dose settingmechanism 4.

If the user decides to replace an empty cartridge and reset the device1, the first and second driver portions 44, 46 must be de-coupled fromone another. After decoupling the first driver portion 44 from thesecond driver portion 46, the first driver portion 44 will be free torotate while the second driver portion 46 will not be free to rotate.

During a device resetting step, rotating the first driver portion 44achieves at least two results. First, rotation of the first driverportion 44 will reset the axial position of the spindle 42 with respectto the dose setting mechanism 4 since rotation of the first driverportion 44 causes the spindle 42 to rotate. Rotation of the spindle 42(because the spindle is splined with the spindle guide 48) moves thespindle in a proximal direction back into the dose setting mechanism.For example, FIG. 7 illustrates one arrangement for connecting thespindle 42 to the spindle guide 48. In FIG. 7, the spindle 42 comprisesa first 51 spline and a second spline 52. The spindle guide 48 comprisesan essentially circular member having an aperture. The aperture includestwo inner protruding members 55, 57 that engage the first and secondsplines 51, 52 respectively, so that the spindle guide 48 locks onto thespindle and rotates along with the spindle during spindle rotation.

Second, rotation of the first driver portion 44 will also axial move orreset a dose limiter 38 to an initial or start position. That is, as thefirst driver portion 44 is rotated back to an initial start position,because the dose limiter 38 is threadedly engaged to the outer grooveand splined to an inner surface of a housing portion, such as the outerhousing 40. In this configuration, the dose limiter 38 is prevented fromrotating but will move along the outer groove 62 of the first driverportion 44 as this portion is rotated during a resetting step. Inaddition, because it is splined to longitudinal splines 65 a, 65 b ofthe outer housing 4, the clicker 75 is also prevented from rotatingduring this resetting step. Referring to a first driver arrangementillustrated in FIG. 3, the two portions of the driver 30 are decoupledwhen the first driver portion 44 is pulled axially away from the seconddriver portion 46. This may be achieved by the use of a biasing means(such as at least one spring) that interacts together when the cartridgeholder 6 is removed from the front or distal end of the device to firstlock the relative rotation between the spindle 42 and a spindle guide 48through which the spindle passes, and then to push this spindle guide 48and also nut 66 axially a fixed distance. Because the spindle 42 isrotationally locked to this spindle guide 48 and is threadedly engagedwith the spindle nut 66, the spindle 42 will move axially.

The spindle 42 is coupled via a groove engaged to the first driverportion 44. The first driver portion 44 is prevented from rotation by aclutched connection to the second driver portion 46. In one preferredarrangement, the second driver portion 46 is prevented from rotation bythe clicker 75 which resides between the clutch and the flange 80 of thedrive sleeve 46. Therefore, axial movement of the spindle 42 decouplesthe two driver portions 44, 46 so that the clutched connection becomesde-coupled.

This sequence of operation as the cartridge holder 6 is removed ordisconnected from the dose setting mechanism 4 is illustrated in FIGS.3-5. In FIG. 3, the various component parts of the drug delivery deviceinclude: a dose setting housing 40, a cartridge 20, a spindle 42, firstdriver portion 44; second driver portion 46, spindle bearing 50, spindleguide 48 spring plate 54; a main spring 60, a pressure plate 64, acartridge holder 20; a spindle nut 66; and a second spring 70. In thispreferred arrangement, the spindle guide 48 is rotationally fixedrelative to the spindle 20. In addition, the spring plate 54 pressureplate 64 and spindle nut 66 are all rotationally fixed relative to theouter housing.

In FIG. 3, the cartridge holder 6 is fitted via apertures in thepressure plate 64 and applies a load to the spring plate 54. Thiscompresses the first biasing means or main spring 60. These apertures inthe pressure plate 64 (not shown) allow the pressure plate 64 to moveaway from the spring plate 54 (in a distal direction towards thecartridge holder 6) under the action of the second biasing means orsecond spring 70. This will open up a Gap “A” as shown in FIG. 3. Gap“A” is a gap created between the pressure plate 64 and the spring plate54. This will also open Gap “B”, a gap between the spindle nut 66 andthe spring plate 54. This Gap B is illustrated in FIG. 3. The Gap B inconjunction with the light force from the second spring or biasing means70 moves the spindle nut 66 towards the distal end of the drug deliverydevice 1. This applies light pressure to the spindle guide 48.

The spindle guide 48 is compressed under the action of the second spring70 between the spindle nut 66 and pressure plate 64. This light forcecoupled with the friction coefficient on either side of a flange of thespindle guide 48 through which this force acts, provides a resistance torotation of the spindle guide 48 and therefore a resistance to rotationof spindle 42 as well. One advantage of this configuration is that atthe end of a dose, it is advantageous to prevent the spindle 42 fromback-winding into the dose setting mechanism 4 under light residualloads that may remain from the cartridge bung 18. By preventing thespindle 42 from back-winding in a proximal direction, a distal end 43 ofthe spindle 42 (and hence the spindle bearing 50) remains on the bung18. Maintaining the distal end 43 of the spindle 42 on the bung 18 helpsto prevent a user from administrating a potential under-dose.

When the user delivers a dose, as the dispense force increases, therearward load on the spindle nut 66 increases to a point at which thespindle nut 66 travels back in a proximal direction and compresses thesecond spring 70. This releases the axial force acting on the spindleguide 48. This removes the resistance to rotation of the spindle guide48 and hence spindle 42. This configuration therefore preventsback-winding of the spindle 42 under low loads caused by the cartridgebung 18 but does not add to the dispense force once this dispense forcehas increased above a certain threshold level.

FIG. 4 illustrates the dose setting mechanism 4 of FIG. 3 with thecartridge holder 6 rotated to release a connection type between thehousing 40 of dose setting mechanism 4 and the cartridge holder 6. Inone arrangement, this connection type 22 is a bayonet connection.However, those of ordinary skill in the art will recognize that otherconnection types 22 may be used as well such as threads, snap locks,snap fits, luer locks and other similar connection types. In thearrangement illustrated in FIGS. 3-5, by rotating the cartridge holder 6with respect to housing 40, features that were initially acting on thespring plate 54 to compress the main biasing means 60 through aperturesin the pressure plate 64, rotate so that they now release this forcecreated by the main biasing means 60. This allows the spring plate 54 tomove in a distal direction until the spring plate 54 contacts thespindle nut 66 on an inside face of the spindle nut 66.

In this second condition, the previous discussed Gap “A” (from FIG. 3)has now been reduced to a Gap “C” (as seen in FIG. 4). In this manner,the relative high axial force from the main biasing means 60 actsthrough the spring plate 54 to the spindle nut 66 and from the spindlenut 66 through the spindle guide 48 to the pressure plate 64. Thisrelative high axial force from the main biasing means 60 is sufficientto prevent the spindle guide 48, and hence spindle 42, from rotating.

After sufficient rotation of the cartridge holder 6, the cartridgeholder 6 disengages from the connection type 22 with the housing 40. Thecartridge holder 6 is then driven in an axial direction away from thehousing 40 by the main biasing means 60 (i.e., in a distal direction).However, during this movement, the main spring 60 continues to load thecartridge holder 6 through the spindle guide 48 and therefore thespindle 42 is prevented from rotation. As the spindle 42 is alsothreaded to the first driver portion 44, the first driver portion 44 isalso pulled axially in a distal direction and in this manner becomesdisengaged from the second driver portion 46. The second driver portion46 is axially fixed and is prevented from rotation. In one arrangement,the second driver portion 46 is prevented from rotation by clickerelements and prevented from axial movement by its axial coupling to thenumber sleeve.

FIG. 5 illustrates the dose setting mechanism illustrated in FIG. 3 in athird position, that is, with the cartridge holder 6 removed. As thecartridge holder 6 is removed from the housing 40, the bayonet featuresshown in FIG. 5 (illustrated as round pegs extending radially inwards oninside of inner housing), limit travel of the pressure plate 64 butallows Gap “C” (as shown in FIG. 4) to increase to a wider Gap “D” (asshown in FIG. 5). As a result, Gap “E” develops. Gap “E” removes thehigh spring force created by the main biasing means 60 from the spindleguide 48. The dose setting mechanism 4 in FIG. 4 is now ready to bereset.

To reset this dose setting mechanism 4, a user retracts the spindle 42in a proximal direction back into the housing 40 by pushing on thedistal end 43 of the spindle 42. Therefore, during this re-setting stepof the dose setting mechanism 4, as the spindle 42 is pushed back intothe dose setting mechanism 4, the movement of the spindle 42 causes thespindle nut 66 to move back against a light spring force created by thesecond biasing means 70. This movement releases the axial load and henceresistance to rotation from the spindle guide 48. Therefore, as the dosesetting mechanism 4 is reset by the spindle 42 rotating back into thedose setting mechanism 4, the spindle guide 48 also rotates.

As the spindle 42 is pushed back further into the dose setting mechanism4, the spindle 42 rotates through the spindle nut 66. As the firstdriver portion 44 is de-coupled from the second driver portion 46, thefirst driver portion 44 rotates (with the flexible elements 102, 103running on a conical surface groove 90 formed by the first annular ring91 on the second half of the drive sleeve 46, FIGS. 5 and 6). Thisaccommodates the axial and rotational movement of the spindle 42.

As the first driver portion 44 rotates during reset, first driverportion 44 also re-sets the dose nut. More specifically, as the firstdriver portion 44 rotates, the dose nut which is not rotatable since itis splined to an inner surface of the housing 40, traverses along thehelical groove 62 provided along an outer surface of the first driverportion 44 and traverses back to an initial or starting position. In onepreferred arrangement, this starting position of the dose nut residesalong the first radial 56 flange of the first driver portion 44.

After the dose setting mechanism 4 has been reset, the dose settingmechanism 4 must be re-connected to the cartridge holder 6. Whenre-connecting these two components, the process generally works inreverse. However, this time the axial compression of the main spring 60causes the first driver portion 44 to re-engage with the second driverportion 46. In this manner, the flexible elements re-engage with thesecond annular ring 94 on the second driver portion 46.

FIG. 6 illustrates a first arrangement of the second driver portion 46and the first driver portion 44 illustrated in FIGS. 3. As shown in FIG.6, second driver portion 46 is generally tubular in shape and comprisesa first annular groove 90 at a distal end of the second driver portion46. The first annular groove 90 comprises a conical face 91. The seconddriver portion further comprises a second annular groove 94 and at leastone spline 96 positioned along a surface of the second driver portion.

The first driver portion 44 is also generally tubular in shape andcomprises a first and a second flexible element 102, 103 and a pluralityof spline recesses 100. These plurality of recesses 100 releasablyconnect the longitudinal spline 96 of the first driver portion 44 tosecond driver portion 46 when both first and second driver portions 44,46 are pushed axially together so that they releasably engage oneanother. When pushed together, the flexible elements 102, 103 of thefirst driver portion 44 are pushed over the first annular groove 90 ofthe second driver portion 46 and then stop when the flange 80 of thesecond driver portion abuts the first axial flange 56 of the firstdriver portion 44.

The first driver portion 44 also includes a plurality of ratchetfeatures 104. These ratchet features 104 are provided at a distal end106 of the first driver portion 44. These ratchet features 104 engagesimilar ratchet features on the spring plate 25 which are splined to thehousing 2. (See e.g., FIGS. 3-5) At the end of the re-setting step,these ratchet features engage one another so as to prevent the firstdriver portion 44 from rotating. This ensures that as the spindle 42 isreset further, the first driver portion moves axially to re-engage thesecond driver portion 46 rather than rotate on the conical face 90.These features also orientate the spring plate 25 relative to the seconddriver portion 44 so that the two driver portions 44, 46 engage easilyduring assembly or after reset. Therefore, these ratchet features alsoprevent the coupling features 100, 96 from clashing with one another.

A second arrangement of resettable dose setting mechanism is illustratedin FIGS. 8-10. FIG. 8 illustrates a section view of a second arrangementof a dose setting mechanism 200. Those of skill in the art willrecognize that dose setting mechanism 200 may include a connectionmechanism for releasably connecting to a cartridge holder, like thecartridge holder 6 illustrated in FIG. 2. However, as those of ordinaryskill in the art will recognize, the dose setting mechanism may alsoinclude a permanent connection mechanism for permanently connecting to acartridge holder. FIG. 9 illustrates a portion of the dose settingmechanism illustrating the driver operation. FIG. 10 illustrates a closeup view of the coupling between the first driver portion and the seconddriver portion illustrated in FIG. 9. The second arrangement of the dosesetting mechanism 200 operates in generally a similar fashion to thefirst arrangement of the dose setting mechanism 4 illustrated in FIGS.1-5.

With reference to FIGS. 8-10, the dose setting mechanism 200 comprises adose dial grip 202, a spring 201, an outer housing 204, a clutch 205, adriver 209, a number sleeve 206, a clicker 220, and an inner housing208. Similar to the driver 30 illustrated in FIGS. 2-5, driver 209 ofdose setting mechanism 200 comprises a first driver portion 207 and asecond driver portion 212. In one arrangement, the first driver portion207 comprises a first component part 210 and a second component part211. Alternatively, the first driver portion 207 is an integralcomponent part.

Where the dose setting mechanism 200 illustrated in FIGS. 8 and 9comprises a resettable dose setting mechanism, the first driver portion207 is de-coupled from the dose setting mechanism 200 when the firstdriver portion 207 is pushed axially towards the second driver portion212 (i.e., pushed in a proximal direction). In one arrangement, this maybe achieved by pushing axially on a distal end of the spindle 214. Thisdoes not require any mechanism associated with removal of a cartridgeholder. The mechanism is also designed such that the first and seconddriver portions 207, 212 remain locked together rotationally during dosesetting as well as during dose administration.

An axial force on the spindle 214 causes the spindle 214 to rotate dueto its threaded connection to the inner housing 208. This rotation andaxial movement of the spindle 214 in turn causes the first driverportion 207 to move axially towards the second driver portion 212. Thiswill eventually de-couple the coupling elements 250 between the firstdriver portion 207 and second driver portion 212. This can be seen fromFIG. 11. This axial movement of the first driver portion 207 towards thesecond driver portion 212 results in certain advantages. For example,one advantage is that the metal spring 201 will compress and willtherefore close the Gap A illustrated in FIGS. 8-10. This in turnprevents the clutch 205 from disengaging from the clicker 220 or fromthe number sleeve 206. As illustrated in FIG. 9, a distal end of theclutch 205 comprise a plurality of clutch teeth 203. These clutch teeth203 engage a plurality of clicker teeth 222 disposed at a proximal endof the clicker 220. As such, when a user dials a dose, these clutch andclicker teeth 203, 222 respectively, engage one another to produce anaudible click (and perhaps a tactile click indication). Preferably, theclicker teeth 222 are geometrically disposed so that each clickcorresponds to a conventional unit dose, or the like. Therefore, whenthe dose dial grip 202 and hence the clutch 205 are rotated, an audiblesound is heard as the clutch teeth ride 203 over the clicker teeth 222.

The second driver 212 is prevented from rotating since it is splined tothe clutch 205. The clicker 220 comprises a plurality of splines 221.These splines 221 are splined to an inner surface of the inner housing208. Therefore, when the Gap A is reduced or closed up, the seconddriver portion 212 cannot rotate relative to either the housing 204 orthe number sleeve 206. As a consequence, the number sleeve 206 cannotrotate relative to the housing 204. If the number sleeve 206 isprevented from rotating then, as the spindle 214 is retracted back intothe dose setting mechanism 200 and thereby re-set, there will be no riskof the number sleeve 206 being pushed out of the proximal side of thedose setting mechanism 200 as a result of a force being applied on thespindle 214.

Similarly, when the drug delivery device is being dispensed, the userapplies an axial load to a dose button 216. The dose dial grip 202 isrotatably coupled to the dial sleeve but non-rotatably coupled to thedose button. The dose button 216 is axially coupled to the clutch 205and this prevents relative axial movement. Therefore, the clutch 205moves axially towards the cartridge end or the distal end of the dosesetting mechanism 200. This movement disengages the clutch 205 from thenumber sleeve 206, allowing for relative rotation while closing up theGap A.

As described above, this prevents the clutch 205 from rotating relativeto the clicker 220 and hence relative to the housing 204. However, inthis scenario, it also prevents the coupling between the first driverportion 207 and the second driver portion 212 from becoming disengaged.Therefore, any axial load on the spindle 214 only disengages the firstand second driver portions 207, 212 when the dose button 216 is notaxially loaded. This therefore does not happen during dispense.

With the dose setting mechanism 200, as a user dials a dose with thedose dial grip 202, the metal spring 201 is selected to be strong enoughto maintain engagement of both clutched couplings: the clutched couplingbetween the clutch 205 and the number sleeve 206 and clutched couplingbetween the first driver portion 207 and second driver portion 212.

FIG. 11 shows in detail of a first arrangement of the first driverportion 207 and the second driver portion 212 illustrated in FIG. 8. Asillustrated in FIG. 11, the second driver portion 212 is generallytubular in shape and comprises at least one drive dog 250 located at adistal end of the second driver portion 212. The first driver portion207 also has a generally tubular shape and comprises a plurality ofrecesses 252 sized to engage with the drive dog 250 on the second driverportion 212. The construction of the drive dog and recesses allowdisengagement with the drive dog 250 when the first and second driverportions are axially pushed together. This construction also creates arotational coupling when these components are sprung apart. A doselimiter may be provided on first driver portion 207 and operatessimilarly to the dose limiter 38 illustrated in FIG. 3.

In this arrangement, the first driver portion 207 comprises a firstportion 211 that is permanently clipped to a second portion 210. In thisarrangement, the first portion 211 comprises the drive dogs 252 and thesecond component 210 includes the outer groove for the last dose nut aswell as an internal groove 254. This internal groove 254 is used toconnect to the spindle 214 and drives the spindle 214 during doseadministration.

In the illustrated arrangement, the internal groove 254 comprises a parthelical groove rather than a complete helical groove. One advantage ofthis arrangement is that it is generally easier to manufacture.

As may be seen from the arrangement illustrated in FIGS. 8-10 there is,in addition, certain feature enhancements over the dose settingmechanism 4 lustrated in FIGS. 3-5. These can be added independently ofthe ability to re-set the device to replace an empty cartridge with anew cartridge. These enhancements, therefore, are relevant to both are-settable and non-re-settable dose setting mechanism.

One of the advantages of both arrangements illustrated but perhaps inparticular in the arrangement illustrated in FIGS. 8-11 is that the dosesetting mechanism 200 has a reduced number of components over otherknown dose setting mechanisms. In addition, apart from the metal coilspring 201 (see FIGS. 9 and 10), all of these components making up thedose setting mechanism 200 may be injection molded using inexpensive andunsophisticated tooling. As just one example, these components making upthe dose setting mechanism 200 may be injection molded without theexpense and sophistication of a rotating core.

Another advantage of a dose setting mechanism 200 comprising an innerhousing 208 such as that illustrated in FIGS. 8-11 is that the dosesetting mechanism 200 can be designed, with a slight modification, as adrug delivery device platform that is now capable of supporting bothre-settable and non-resettable drug delivery devices. As just oneexample, to modify the re-settable dose setting mechanism 200 variantillustrated in FIGS. 8-11 into a non-resettable drug delivery device,the first driver portion 211 and 210 and the second driver portion 212can be molded as one unitary part. This reduces the total number of drugdelivery device components by two. Otherwise, the drug delivery deviceillustrated in FIGS. 8-11 could remain unchanged. In such a disposabledevice, the cartridge holder would be fixed to the housing oralternatively, made as a single one piece body and cartridge holder.

The illustration in FIGS. 8-11 shows an inner housing 208 having alength “L” 230 generally similar in overall length to the dose settingmechanism 200. As will be described, providing the inner housing 208with a length of “L” has a number of advantages over other known dosesetting mechanisms that do not utilize an inner body or an inner bodyhaving a length generally equal to that of the length of a dose settingmechanism.

The inner housing 208 comprises a groove 232 provided along an externalsurface 234 of the inner housing. A groove guide 236 provided on aninner surface 238 of the number sleeve 206 is rotatably engaged withthis groove 232.

One advantage of this dose setting mechanism 200 utilizing the innerhousing 208 is that the inner housing 208 can be made from anengineering plastic that minimizes friction relative to the numbersleeve 206, groove guide 236 and the groove 232. For example, one suchan engineering plastic could comprise Acetal. However, those of ordinaryskill in the art will recognize that other comparable engineeringplastics having a low coefficient of friction could also be used. Usingsuch an engineering plastic enables the material for the outer housing204 to be chosen for aesthetic or tactile reasons with no frictionrelated requirements since the outer housing 204 does not engage anymoving components during normal operation.

The inner housing 208 also enables the number sleeve 206 to be providedwith a helical groove on an inner surface 238 of the number sleeve 206,rather than providing such a helical groove on an external surface 240of the number sleeve 206. Providing such an internal groove results in anumber of advantages. For example, this results in one advantage ofproviding more surface area along the outer surface 240 of number sleeve206 so as to provide the scale arrangement 242. Increased number sleevesurface area may be used for drug or device identification purposes.Another advantage of providing the helical groove 236 on the innersurface 238 of the drive sleeve 206 is that this inner groove 236 is nowprotected from dirt ingress. In other words, it is more difficult fordirt to become logged in this inner groove interface than if the groovewere provided along the outer surface 240 of the number sleeve 206. Thisfeature is particularly important for a re-settable drug delivery devicewhich will have to function over a much longer period of time comparedto a non-resettable device. The effective driving diameter (representedby ‘D’) of the grooved interface between the number sleeve 206 and theinner housing 208 is reduced compared to certain known drug deliverydevices for the same outer body diameter. This improves efficiency andenables the drug delivery device to function with a lower pitch(represented by ‘P’) for this groove and groove guide connection. Inother words, as the helix angle of the thread determines whether whenpushed axially, the number sleeve will rotate or lock to the inner bodywherein this helix angle is proportional to the ratio of P/D.

The number sleeve 206 can be made the length of the mechanism “L” 230rather than having to split this length into the space required for thenumber sleeve 206 and a space required for a clicker and a dose limiter.One advantage of this configuration is that it ensures a good axialengagement between the number sleeve 206 and the outer housing 204. Thisimproves the functionality (and perceived quality) of the dose settingmechanism when a user uses the drug delivery device to dial out amaximum settable dose. FIG. 13 illustrates the dose setting mechanism200 dialed out to a maximum settable dose of 80 International Units(“IU”).

Another advantage is that it enables the scale arrangement 242 to behidden within the outer housing 204 even when the number sleeve 206 isfully dialed out as may be seen from FIG. 13. However, the design doesnot limit the position of the window 14 to that shown in FIG. 8 butallows this window 14 to be positioned at near the dose dial grip 202 ofthe device. In arrangements illustrated in FIGS. 12 and 13, the scalearrangement 242 will only be visible by way of the window 14.

Also the driver 209 (whether made in two portions or just one unitarycomponent) can be made with a plain internal through hole plus a threadform that can be molded with axially moving core pins. This avoids thedisadvantage of a driver having an internal thread with more than oneturn and therefore requires a core pin to be rotated out several turnsduring a de-molding process.

One potential disadvantage of utilizing a dose setting mechanismcomprising the inner housing 208 is that the use of the inner housing208 adds a component part to the overall dose setting mechanism 200.Consequently, this inner housing 208 will tend to increase the overallwall thickness that must be designed to fit between the clutch 205 andnumber sleeve 206. One way to work around this design issue, asillustrated in FIG. 8, is to reduce the diameter of the clutch 205 andnumber sleeve 206. This in turn can be achieved because the thread formbetween the driver 209 and the spindle 214 comprises a male internalfeature on the driver 209 and a female external groove form on thespindle 214 that are overlapping with (on a similar diameter with) thespindle groove form that interfaces with the groove along the innersurface 234 of the inner housing 208 or body portion.

The overlapping of groove forms on the spindle 214 reduces the effectivediameter of the thread interface with the driver 209. This also reducesthe potential outer diameter of the driver 209 enabling the addition ofthe inner housing 208 without increasing the overall outer diameter ofthe dose setting mechanism 200. Another added benefit of the reducedeffective diameter of the thread interface with the driver 209 is thatit improves efficiency of the drug delivery device during dispense asexplained above. The window 244 through which the scale arrangement 242may be viewed can either be just an aperture in the outer housing 204 orcan include a clear lens or window designed to magnify the scalearrangement (i.e., printed or laser marked dose numbers) along a portionof the outer surface 240 on the number sleeve 206. The connection of acartridge holder into the outer housing 204 can be achieved using eithera screw or bayonet type connection. Alternatively, any similarly robustdesign used in drug delivery devices requiring a largely cylindricalpart to be removed and then reattached could also be used.

With the limited choice of mechanical advantages available with theoverlapping helical spindle 214 in the arrangement illustrated in FIGS.8-11, often an optimum choice of mechanical advantage for the length ofthe dose setting mechanism (and hence overall length of the drugdelivery device) required is difficult to achieve. Hence, an alternativearrangement for this dose setting mechanism having a multi-componentdrive sleeve may be desired. Therefore, there may be a need for anenhanced dose setting mechanism that enables a mechanical advantage tobe varied without changing the ratio of the pitches of the grooves onthe spindle, such as the multi-groove spindle illustrated in FIGS. 8-10.Such an enhanced dose setting mechanism is illustrated in FIGS. 14 and15.

For example, FIG. 14 illustrates a sectional view of another embodimentof a dose setting mechanism of the drug delivery device illustrated inFIG. 1. FIG. 15 illustrates a partial sectional view of the embodimentof the dose setting mechanism illustrated in FIG. 14. This alternativearrangement of the dose setting mechanism 300 operates in generally asimilar fashion to the dose setting mechanism 200 illustrated in FIGS.8-11. That is, the dose setting and dose injecting operations aregenerally the same. One difference between these two dose settingmechanisms, however, is in what occurs when a user resets the dosesetting mechanism 300. With reference to FIGS. 14 and 15, the dosesetting mechanism 300 comprises a dose dial grip 302, a spring 301, anouter housing 304, a clutch 305, a driver 309, a number sleeve 306, aclicker 375, a dose limiter 318, and an inner housing 308. Similar tothe driver 209 illustrated in FIGS. 8-11, driver 309 of dose settingmechanism 300 comprises a first driver portion 307 and a second driverportion 312. In one arrangement, the first driver portion 307 comprisesa first component part 310 and a second component part 311 (seegenerally, FIG. 11). Alternatively, the first driver portion 307 is anintegral component part.

Where the dose setting mechanism 300 illustrated in FIGS. 14 and 15comprises a resettable dose setting mechanism, the first driver portion307 is de-coupled from the dose setting mechanism 300 when the firstdriver portion 307 is pushed axially towards the second driver portion312 (i.e., pushed in a proximal direction). This does not require anymechanism associated with removal of a cartridge holder. The mechanismis also designed such that the first and second driver portions 307, 312remain locked together rotationally during dose setting as well asduring dose administration.

Returning to the arrangements illustrated in FIGS. 8-10, themulti-component driver 209 moves axially without rotation relative tothe internal housing 208 during dose dispense. In the alternativearrangement illustrated in FIGS. 14-15, the driver 309 does not justmove axially during dispense but is constrained to move along a helicalpath. Such a helical path may be defined by one or more helical splines341 molded into an inner surface of the inner housing 308. In such anarrangement, the path of the driver 309 may be controlled through arotational coupling between a clicker 375 (preferably, by way of asecond clicker portion 377) with at least one helical groove 341provided along an inner surface of the inner housing 308.

If these helical grooves provided along the inside of the inner housing308 rotate in the opposite sense to the thread form on the first driverportion 307 or the number sleeve 306, then the mechanical advantage maybe reduced. However, if these helical grooves rotate in the same senseto the thread form on the first driver portion 307 or the number sleeve306, and with a larger pitch, then the mechanical advantage may beincreased.

With such a proposed dose setting mechanism 300, an equation for theresulting mechanical advantage may be calculated via the followingequation: (A+B)/[A×(1−B/C)]. In this equation, A is the groove pitchbetween the spindle 314 and inner housing 308, B is the groove pitchbetween the spindle 314 and the first driver portion 307, and C is thepitch of the helical grooves 341 with a positive notation depicting inthe same sense as B.

In this arrangement and as illustrated in FIGS. 14 and 15, the clicker375 comprises a multi-component clicker. Specifically, clicker 375comprises a first clicker portion 376 and a second clicker portion 377.The first and second clicker portions 376, 377 comprise clicker teeth378 and 377, respectively. Both first and second clicker portions 376,377 are placed on a distal side of the metal coil spring 301. This is incontrast to the location of the clicker in the dose setting mechanism200 illustrated in FIG. 8. In the arrangement illustrated in FIG. 8, theclicker arrangement 220 is positioned on a proximal side of the spring201.

Positioning the clicker 375 on the distal side of the metal coil spring301 achieves a number of advantages. For example, it helps to ensurethat the second clicker portion 377 that is rotationally coupled to thehelical grooves provided along the inner housing 308 does not moveaxially and hence does not rotate relative to the housing when thebutton 316 is depressed to thereby disengage the clutch 305 from thenumber sleeve 312. If the clicker 375 were allowed to rotate, theclicker 375 would cause the clutch 305 to rotate. If this were to occur,this may prevent the clutch 305 from re-engaging with the dose dialsleeve 306 at the end of dose. Also, if the clutch 305 were allowed torotate when the button 316 is depressed, the driver 309 would rotate aswell and this would affect dose accuracy when a user releases the button316 and the driver 309 rotates.

Again, with this alternative arrangement of a dose setting mechanism300, rather than having the clicker teeth between the clicker 375 andthe first driver portion 307, the clicker 375 has been split into twoparts 376, 377. In this arrangement, the first driver portion 307 canrotate on a circular bearing surface during resetting of the spindle 314and the clicker teeth are instead placed between the first and secondclicker portions 376, 377, respectively. The first clicker portion 376may be rotationally coupled to either the driver 309 or the clutch 305.Therefore, during dose dialing, the first clicker portion 376 rotatesrelative to the second clicker portion 377 which is rotationally coupledto the helical grooves 341 in the inner housing 308 as mentioned above.Also in this arrangement where it is the first clicker portion 376 thatoscillates axially (in a proximal direction and then a distal direction)during dialing the clicker teeth 378, 379 can be symmetric. On advantageof symmetrical clicker teeth is that the user is provided with a similartactile response when he or she is either dialing up a dose comparedwith dialing down a dose. If the first clicker portion 376 were to berotationally coupled to the inner housing 308, as this first clickerportion 376 oscillated proximally and distally during dialing it wouldalso oscillate rotationally. One perceived disadvantage of such anarrangement is that the resulting dialing torque would be substantiallydifferent when the user would be dialing up to dialing down a dose. Notethat with the dose setting arrangement 300 illustrated in FIGS. 14 and15, the number of clicker teeth on the first and second clicker portions376, 377 has to be altered to account for the thread pitches B and C inorder to get the correct number of clicks per rotation to match thenumbers or other similar dose setting indicia provided on the dose dialsleeve 312. In addition, the dose limiter 318 also comprises splines 333that run in the same helical grooves 341 in the inner housing 308 as thesecond clicker portion 377. Therefore, during dose dispense, the doselimiter 318 will not rotate relative to the driver 309 thereby ensuringthat no further doses can be dialed after the dose limiter 318 has comeup against a stop on the first driver portion 307. Similar to the driverillustrated in FIGS. 8-11, the first driver portion 307 of dose settingmechanism 300 comprises two parts clipped together.

Although the dose setting mechanism 300 illustrated in FIGS. 14 and 15provides a number of advantages, there are also certain limitationsassociated with such an arrangement. For example, one issue with dosesetting mechanism 300 is that when mechanism is reset so as to replace aused cartridge, the spindle 314 is pressed back proximally. Pressing thespindle back proximally moves the first driver portion 307 and hence theclicker 375 proximally relative to the outer housing 304. If the clicker375 moves relative to the housing 304, then the clicker 375 also has torotate. Therefore, during the resetting step, the first driver portion307 not only compresses the spring 301 but has to rotate the clicker 375and hence driver 309, the clutch 305, and dose dial sleeve 306 relativeto the housing 304. This increases the force required to reset the dosesetting mechanism 300.

FIG. 16 illustrates a partial view of yet another embodiment of a dosesetting mechanism of the drug delivery device illustrated in FIG. 1. Inthis illustration, the dose setting mechanism 400 is illustrated with adose setting button pressed in. FIG. 17 illustrates the partialsectional view of embodiment of the dose setting mechanism 400illustrated in FIG. 16 in a second position with the dose setting buttonbeing pressed out. FIG. 18 illustrates the partial sectional view ofembodiment of the dose setting mechanism 400 illustrated in FIG. 17 witha second clicker portion 477 removed.

The alternative embodiment of the dose setting mechanism 400 comprises aclutch 405, a clicker 475, and a spring 401. As shown in FIG. 16, theclicker 475 comprises a first clicker portion 476 and a second clickerportion 477. In this arrangement, the first clicker portion 476 issimilar to the clicker illustrated in FIGS. 8-11 in that the firstclicker portion 476 comprises a plurality of clicker teeth 422. Theseclicker teeth 422 engage a plurality of clutch teeth 403.

However, unlike the clicker 220 of FIG. 8 comprising splines that engagethe helical groove 241 provided on the inner housing 208, the firstclicker portion 476 of dose setting mechanism 400 is not splined to aninner housing. Rather, the second clicker portion 477 is rotationallycoupled to the first clicker portion 476, axially coupled to the driver409 and rotationally coupled to the helical grooves provided on an innerhousing. In this dose setting mechanism 400 arrangement, neither thedriver 409, the clutch 405, nor clicker rotate, when a dose button isdepressed. Similarly, neither the driver 409, the clutch 405, nor theclicker rotate when the dose setting mechanism 400 is reset. Oneadvantage of such an arrangement is that this mechanism ensures a lowforce to reset the pen and good dose accuracy.

FIG. 19 illustrates the second clicker portion 477 that may be used withthe dose setting mechanism illustrated in FIG. 16. As can be seen fromFIG. 19, the second clicker portion 477 comprises a plurality of splines480 that engage a helical groove provided along an inner surface of theinner housing. In addition, the second clicker portion 477 furthercomprises a recess 482. This recess 482 engages a rib provided on thesecond driver portion 412. When this recess 482 engages this rib, thesecond clicker portion 477 is axially secured to the second driverportion 412.

In particular, the various clicker arrangements shown in embodiments200, 300 and 400 can be mounted either internally to the inner body, asshown, or externally, with ribs or grooves in the clicker engaging withribs or grooves on the outer surface of the inner body or as shown inthe first embodiment (ref FIGS. 3-5) on the inner surface of the outerbody. Where an inner body exists, in these alternative arrangements theclutch, spring and clicker components would have to lie outside theinner body, but the driver could still be rotationally coupled to theclutch and lie inside the inner body so as to drive the spindleforwards.

Exemplary embodiments of the present invention have been described.Those skilled in the art will understand, however, that changes andmodifications may be made to these embodiments without departing fromthe true scope and spirit of the present invention, which is defined bythe claims.

1. A dose setting mechanism for a drug delivery device, said mechanismcomprising: an outer housing; an inner housing having an externalgroove, said inner housing configured to guide said driver to dispense adose set by said dose setting mechanism; and a dial sleeve disposedbetween said outer housing and said inner housing, said dial sleeverotatably engaged with said external groove of said inner housing;wherein said dial sleeve is configured to rotate with respect to bothsaid outer housing and said inner housing during dose setting andconfigured to be translated away from both said outer housing and saidinner housing, characterized in that the inner housing comprises aninternal helical spline.
 2. The dose setting mechanism according toclaim 1 wherein said internal helical spline is configured to guide saiddriver in a helical motion during dose dispense.
 3. The dose settingmechanism according to claim 1 wherein said driver comprises a firstdriver portion and a second driver portion, wherein said first or saidsecond driver portion preferably comprise a plurality of drivercomponents.
 4. The dose setting mechanism according to claim 1 furthercomprising a dose limiter, said dose limiter splined to said helicalspline of said inner housing.
 5. The dose setting mechanism according toclaim 4 wherein said dose limiter comprises an internal helical groovethat is operatively coupled to a helical groove provided on said driver.6. The dose setting mechanism according to claim 1 further comprising aclicker
 7. The dose setting mechanism according to claim 6 wherein saidclicker guides said driver in a helical motion and wherein said clickerresides within said inner housing.
 8. The dose setting mechanismaccording to claim 6 wherein said clicker comprises a first clickerportion and a second clicker portion, wherein said first clicker portioncomprises a first set of clicker teeth that are configured for engaginga second set of clicker teeth of said second clicker portion.
 9. Thedose setting mechanism according to claim 6 wherein said clicker or saidfirst clicker portion comprises said at least one spline configured toengage said helical spline of said inner housing.
 10. The dose settingmechanism according to claim 6 wherein said clicker comprises a firstset of clicker teeth that are rotationally engaged with a clutch. 11.The dose setting mechanism according to claim 6 wherein said clicker isaxially secured to said driver.
 12. The dose setting mechanism accordingto claim 6 wherein said clicker is configured to rotate during a dosesetting step and/or to rotate during a dosing step and/or, said dosesetting mechanism comprising a resettable dose setting mechanism, torotate during a resetting step.
 13. The dose setting mechanism accordingto claim 1 further comprising a spindle, said spindle operativelycoupled to said driver such that when said inner housing guides saiddriver to dispense said dose set by said dose setting mechanism, saiddriver pushes said spindle to act on a cartridge bung while said spindletranslates in a distal direction to expel said dose from said cartridge.14. The dose setting mechanism according to claim 13 wherein saidspindle comprises a first and a second helical groove.
 15. The dosesetting mechanism according to claim 13 wherein said spindle isconfigured not to rotate during a dose setting step and/or to rotateduring a dosing step and/or to rotate during a resetting step.
 16. Adose setting mechanism for a drug delivery device, said mechanismcomprising: an outer housing: an inner housing having an external grooveand a helical spline, wherein said helical spline of said inner housingis positioned on an internal surface of said inner housing a dial sleevecoupled to said external groove of said inner housing; a driverrotationally coupled to said dial sleeve during a dose setting step: acoupling member comprising at least one rib that is rotationally coupledto said helical spline of said inner housing: such that when during saiddose setting step, said dial sleeve and said driver are both rotated,said dial sleeve follows said external groove on said inner housing, andsaid coupler rotates out on said helical spline and is allowed to rotaterelative to said dial sleeve and driver; and during a dose dispensestep, said driver is rotationally decoupled from said dial sleeve androtationally coupled with said coupler, characterized in thatcharacterized in that said coupler is configured not to move axiallyrelative to said inner housing and not to rotate said driver when saiddose setting mechanism is moved between said dose setting step and saiddose dispense step or between said dose dispense step and said dosesetting step.